The fundamental question of how parathyroid cells sense and respond to changes in the concentration of extracellular ionized calcium forms the basis for these proposed studies. Intracellular microelectrode recording from parathyroid cells has revealed a unique and striking dependence of the transmembrane potential on the concentration of extracellular calcium (Bruce and Anderson, 1979) where increasing stimulus strength (i.e. hypocalcemia) induced membrane hyperpolarization. Furthermore, this hyperpolarizing response occured in a sigmoidal fashion over a relatively narrow range of calcium concentrations suggestive of the calcium sensitivity of the PTH secretory response observed in cattle (Blum et al., 1974). The present studies are designed to: (1) test the hypothesis that the low calcium induced membrane hyperpolarization is an expression of the cell membrane calcium sensing mechanism. These studies will correlate the secretion of PTH with intracellular microelectrode recordings, (2) to test the hypothesis that the increased potassium conductance, which appears to account for the hyperpolarizing response to low calcium, occurs as a result of decreased calcium screening and/or binding to negative membrane surface charges. These studies will include cell electrophoresis techniques to evaluate surface charge under different experimental conditions as well as correlation of PTH secretion with experimental purtabations known to influence surface charge. Through the combined forces of these different techniques, it is hoped that new insight into this long standing endocrine problem will be realized as well as new information on the role of cell membrane surface charge as a transducer of environmental signals into cellular responses.